Drug Interaction Report

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of P-glycoprotein (P-gp), such as dabigatran. The proposed mechanism is isavuconazole inhibition of P-gp-mediated efflux of these drugs.

MANAGEMENT: Caution is advised if isavuconazonium sulfate is used concomitantly with drugs that are substrates of P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever isavuconazonium sulfate is added to or withdrawn from therapy with these drugs. Patients receiving concomitant dabigatran should be monitored closely for the development of bleeding complications and the dosage of dabigatran adjusted as necessary.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of trametinib. In study subjects, administration of a single dose of trametinib with a high-fat, high-calorie meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 70% and 24%, respectively, and delayed Tmax by approximately 4 hours compared to administration in the fasted state.

MANAGEMENT: Trametinib should be taken at least 1 hour before or 2 hours after a meal.